Anti-Relapse effects of donor natural killer cells and IL-2 gene modification on allogeneic hematopoietic stem cell transplantation in acute leukemia.

Abstract

Patients with acute leukemia (AL) refractory to induction or reinduction chemotherapy show poor prognoses if they do not undergo allogeneic hematopoietic stem-cell transplantation (AHSCT). The present study aims to investigate whether donor natural killer (NK) cells and interleukin-2 (IL-2) gene modification exert anti-relapse effects on AHSCT after establishing a mouse model of AL. C57BL/6 (H-2b) mice were selected as donor mice to obtain NK cells and hematopoietic stem cells, while BALB/c (H-2d) mice were selected as the recipient mice for AHSCT. The AHSCT-treated mice were then injected with the donor NK cells, recombinant adenovirus expressing IL-2 (AdIL-2), or the NK cells infected by AdIL-2. Flow cytometry was performed to detect the cell transplantation rate, immune cell number, and cell immunogenicity. Enzyme-linked immunosorbent assay (ELISA) was employed to quantify the secretion of IL-2 in spleen cells, and the level of peripheral blood factors, including interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), IL-35, transforming growth factor β (TGF-β), and IL-10. In our experiments, promotional effects of NK cells and AdIL-2 were found on cell transplantation rate, immune reconstitution ability, cell immunogenicity, IL-2 secretion, as well as increased peripheral blood factor levels in the recipient mice treated with AHSCT, with improved pathological changes observed. Moreover, the aforementioned changes were further promoted in the AHSCT-treated recipient mice injected with the AdIL-2-infected NK cells. These results uncover that the donor NK cells and IL-2 gene modification could inhibit the relapse of AL mice underwent AHSCT, hereby providing a new target for leukemia treatment.